International Journal of Pharmaceutics 327 (2006) 12–16 Stability of cosmetic formulations containing esters of Vitamins E and A: Chemical and physical aspects International Journal of Pharmaceutics 327 (2006) 12–16

Introduction: Read from the article Aim: The aim of this study was to validate chemical and physical methods for stability determination in cosmetic formulations, using a gel-cream containing retinyl palmitate and tocopheryl acetate as a model. The results should also contribute to a better understanding of physical and chemical stability aspects of cosmetic formulations, mainly if they contain derivatives of Vitamins A and E.

Materials Vitamin A palmitate (1,000,000 UI/g), Vitamin E acetate and Vitamin K1, Solvents,…. Methods Gel-cream formulation, Stability studies: Formulations containing vitamins A and E, were stored in PVC pots at 45, 37 and 25 ◦C and 75% relative humidity for up to 120 days. Samples collected at 7-day intervals during the first 28 days and 60 and 120 days later for physical and chemical examination. Chemical Stability testing for the vitamins using HPLC method and Calculations of shelf-life using the Arrhenius equation.

Rheological measurements Physical stability was assessed through rheological determinations performed in a Brookfield rotational rheometer with a cone-plate configuration, connected to a Brookfield software program. Rheological parameters were determined at 25 ◦C, using 0.5 g of each sample, 24 h after preparation and after different storage times. Rheogram curves constructed with ascendant and descendant segmentsm were obtained with rotation speeds increasing progressively (1–4 rpm) and gradually decreasing (4–1 rpm).

With the results obtained, values for consistency index (related to the system viscosity) and flow index (related to the system pseudoplasticity) were mathematically calculated by the Ostwald law: where τ is the shear stress, κ the consistency index, γ the shear rate, η is the flow index.

Results and discussion Fig2. Quantification, expressed as logs of concentration values over time, of (A) : retinyl palmitate and (B): tocopheryl acetate, in formulations maintained at room temperature (25 ◦C), 37 or 45 ◦C with 75% relative humidity.

it is known that Vitamin A Retinyl palmitate had a lower stability than tocopheryl acetate (Fig. 2), indicating Vitamin A as the limiting factor in the calculation of product shelf-life. Furthermore, if retinyl palmitate decomposition leads to a complex mixture of products, its toxicity must also be considered. Thus, shelf-life determination is essential not only for efficacy aspects, but also to evaluate formulation toxicity.Thus, the safety and efficacy the system proposed in this study is acceptable only if the product is to be used in a restricted period of time.

Rheological measurements carried out in parallel with chemical studies represent a complete, rational and necessary approach to predict physical sample behavior during expected shelf-life. Rheological parameters indicated that addition of vitamins to the basic formulation did not compromise its structure but altered some of the rheological parameters as shown in rheogram (A) in (Fig. 3). The flow index in all formulations was below 1 indicating pseudoplasticity, which is a desirable rheological property in these preparations. It was not significantly altered despite a significant decrease in the consistency index after additions of retinyl palmitate and tocopheryl acetate. Fig. 3. Formulation rheograms, 24 h after preparation at room temperature. Formulations containing or not vitamins were compared in both time periods.

physical alterations are more prominent in formulations with added vitamins. Accordingly, Fig. 3B illustrates alterations of physical stability in the formulations containing vitamins, such as thixotropy, in addition to flow and consistency indexes. Fig. 3. Formulation rheograms 120 days after preparation (B) at room temperature. Formulations containing or not vitamins were compared in both time periods.

This instability was not seen in the formulations without vitamins, suggesting that vitamin instability affected the formulation physical Integrity. Rheological parameters were determined and compared in formulations kept at different temperatures after 15% of the Vitamin A was degraded. Results are shown in Fig. 4 and Table 3. Rheological characteristics of formulations with approximately 85% of retinyl palmitate at all storage conditions were similar. It is concluded that accelerated physical stability studies by rheological measurements were also validated.

Although flow indexes were not altered by thermal stress consistency indexes increased significantly (Table 3). It is widely known that consistency indexes normally decrease during storage, indicating instability, but in our results the consistency index increased. It is possible that this was due to the interaction of retinyl palmitate and polyacrilamide, the vehicle polymer. Table 3: Consistency (CI) and flow index (FI) values determined in formulations 24 h after preparation and after 15% degradation of retinyl palmitate Fig. 4. Formulation rheograms after 15% degradation of Vitamin A. Analyses were performed after (1) 77 days at 25 ◦C, (2) 21 days at 37 ◦C and (3) 14 days at 45 ◦C.

Conclusion It is concluded that the results in the present study validate chromatographical and rheological methods for analysis of gel-cream stability. Rheology measurements are simple and effective means to compare properties over time and HPLC furnishes accurate quantitative data on different substances added to complex matrixes. In addition, the results contribute to the understanding of cosmetic stability in formulations containing retinyl palmitate and tocopheryl acetate and confirm that chemical and physical stability must be evaluated at the same time since they seem to have related effects.